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  • 1.
    Drott, Carl Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Franzén, Petra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Ghrelin in rat pancreatic islets decreases islet blood flow2019In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 317, no 1, p. E139-E146Article in journal (Refereed)
    Abstract [en]

    The peptide ghrelin is mainly produced in some of the epithelial cells in the stomach, but also, during starvation, by the epsilon-cells in the endocrine pancreas. Ghrelin, as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1 alpha). exerts a variety of metabolic functions including stimulation of appetite and weight gain. Its complete role is not yet fully understood, including whether it has any vascular functions. The present study evaluated if ghrelin affects pancreatic and islet blood flow. Ghrelin and the GHS-R1 alpha receptor antagonist GHRP-6 were injected intravenously in rats followed by blood flow measurements using a microsphere technique. Ghrelin decreased, while GHRP-6 in fasted, but not fed, rats selectively increased islet blood flow fourfold. GHS-R1 alpha was identified not only on glucagon-producing cells but also seemed to be present in the islet arterioles. GHRP-6 in fasted rats. only, also improved the peak insulin response to glucose in vivo. thereby substantially blunting the hyperglycemia. GHRP-6 doubled glucose-stimulated insulin release in vitro of both islets obtained from fed and fasted rats. Our results indicate a novel role for endogenous ghrelin acting directly or indirectly as a local vasoconstrictor in the islets during fasting, thereby restricting the insulin response to hyperglycemia. This is to the best of our knowledge the first report that shows this physiological mechanism to restrict insulin delivery from the islets by acting on the vasculature; a mode of action that can be envisaged to complement the previously well-described mechanisms of ghrelin acting directly on the islet endocrine cells.

  • 2.
    Drott, Carl Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Franzén, Petra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ghrelin in rat pancreatic islets decreases islet blood flow and impairs insulin secretion2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S218-S218Article in journal (Other academic)
  • 3. Öhlund, Malin
    et al.
    Franzén, Petra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Andersson, Göran
    Ström Holst, Bodil
    Lau, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Laser Microdissection of Pancreatic Islets Allows for Quantitative Real-Time PCR Detection of Islet-Specific Gene Expression in Healthy and Diabetic Cats2014In: Journal of Gastroenterology, Pancreatology & Liver Disorders, ISSN 2374-815X, Vol. 1, no 4, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Background: Feline diabetes mellitus shares many similarities with human type 2 diabetes mellitus, including clinical, physiological and pathological features of the disease. The domestic cat spontaneously develops diabetes associated with insulin resistance in their middle age or later, with residual but declining insulin secretion. Humans and cats share largely the same environment and risk factors for diabetes, such as obesity and physical inactivity. Moreover, amyloid formation and loss of beta cells are found in the islets of the diabetic cat, as in humans. Altogether, the diabetic cat is a good model for type 2 diabetes in humans. The aims of the present study were to isolate feline islets using laser microdissection and to develop a quantitative method for detection of mRNA levels in islets of healthy and diabetic cats.Results: By using the laser microdissection technique, we were able to meticulously sample islets from both healthy and diabetic cats. Insulin staining of separate sections showed many beta cells in islets from healthy cats, whereas few insulin positive cells were found in islets from diabetic cats. By quantitative real-time PCR, mRNA levels of the islet-specific genes INS, PDX1IAPPCHGA and IA-2could be detected in both healthy and diabetic cats.Conclusions: Laser microdissection allows distinct studies of islets without contamination of acinar cells. Previous attempts in isolating feline islets with different collagenase-based protocols have led to damaged islets or islets coated with exocrine acinar cells, which either way compromise the results obtained from gene expression studies. The use of the laser microdissection technique eliminates these problems as shown in this study. Differences in gene expression between healthy and diabetic cats can reveal underlying mechanisms for beta cell dysfunction and decreased beta cell mass in human type 2 diabetes.

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